Retrospective analysis of 30mg/kg ATLG in preventing GVHD after haploidentical hematopoietic stem cell transplantation

Abstract

Abstract Background: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has emerged as a critical treatment option for patients with hematologic malignancies, particularly in cases where an HLA-matched donor is unavailable. Graft-versus-host disease (GVHD) is a significant complication that can drastically impact survival and quality of life post-transplant. Anti–T lymphocyte globulin (ATLG) has shown efficacy in depleting T cells and preventing GVHD, although its optimal dosing remains a topic of debate. To retrospectively evaluate the clinical efficacy and safety of using 30mg/kg ATLG for GVHD prophylaxis in haplo-HSCT, we will focus on GVHD incidence, relapse rates, non-relapse mortality, and overall survival. We aim to provide further insight into optimizing GVHD prophylaxis and improving long-term patient outcomes in haplo-HSCT. Method: A total of 84 patients who underwent haplo-HSCT between May 2017 and June 2024 in Zhujiang hospital were included in the analysis, including acute lymphoblastic leukemia (n=36, 42.8%), acute myeloid leukemia (n=39, 46.4%), T lymphoblastic lymphoma (n=4, 4.8%), myelodysplastic syndrome (n=3, 3.6%), acute biphenotypic leukemia (n=1, 1.2%), and chronic myelogenous leukemia (n=1, 1.2%). Among the patients, 74 (88.1%) were in complete remission before transplantation, while 11 (11.9%) were in non-complete remission. The median age was 33 years (11-67). All patients received 30mg/kg ATLG during transplantation for GVHD prophylaxis. Results: The median follow-up time was 18 months (range, 1-89). The three-year cumulative overall survival (OS) rate was 71.4%, and the three-year disease-free survival (DFS) rate was 59.7%. The median OS was not reached, while the median DFS was 71 months. Subgroup analysis revealed a significant difference in cumulative survival rates between the complete remission and non-complete remission groups before transplantation, with OS in the complete remission group significantly higher than that in the non-complete remission group (p<0.0001). The cumulative three-year relapse rate was 31.4%. The cumulative non-relapse mortality rate was 12.2%, with all cases occurring within 8 months post-transplant. Of these, 30% were related to uncontrolled infections, 30% to severe aGVHD, 20% to thrombotic microangiopathy, 10% to hepatic veno-occlusive disease, and 10% to cerebral infarction. The cumulative incidence of aGVHD was 52.8%, with grade 2-4 and grade 3-4 aGVHD at 21.7% and 8.6%, respectively. The three-year cumulative incidence of cGVHD was 55.1%, with extensive cGVHD occurring in 13.0% of cases. The 180-day reactivation rates of cytomegalovirus and Epstein-Barr virus were 65.5% and 15.7%, respectively. Conclusion: The results of this study support 30mg/kg ATLG as an effective and safe strategy for preventing GVHD in haplo-HSCT. This approach significantly reduces the incidence of severe aGVHD without increasing non-relapse mortality, severe infections, or relapse rates, while ensuring favorable long-term survival outcomes and minimal transplant-related complications.